Of the four Plasmodium species generally responsible for human malaria, Plasmodium falciparum produces the most severe disease and almost all deaths. P. falciparum also has become resistant to chloroquine, once the first-line drug for the prophylaxis and treatment of malaria, so that death rates are returning to historic levels in many areas of Africa. Research in the Malaria Genetics Sections is conducted to understand the factors that determine the drug responses, virulence and transmission of P. falciparum malaria and thereby provide a foundation for new diagnostics and therapeutic measures against the disease. Current efforts include projects on 1) the mechanism of chloroquine resistance in Plasmodium falciparum malaria; 2) alternative antimalarial compounds that block the dihydrofolate-reductase (DHFR) target of the drugs pyrimethamine and cycloguanil; 3) the expression and variation of the var gene family that modulates the adhesive and antigenic character of parasitized red blood cells; 4) occurrence of severe malaria in African children who carry the hemoglobin C mutation; and 5) a genetic defect of chromosome 12 that adversely affects the development of male gametocytes.